Project Abstract This research project directly support NIOSH research objectives focused on the ?development of methods for measuring early markers of adverse health effects?, with a specific focus on novel technologies for quantitative non-invasive biomonitoring. More specifically, this project directly targets the needs of the Agricultural Industry Sector where NIOSH has identified pesticide exposure as a high research priority. In addition, the proposal specifically addresses the Cross Sector- Exposure Assessment Strategic Goal #2 that is focused on, the development and/or improvement of specific methods and tools to assess worker exposures to critical occupational agents and stressors. These NIOSH research objectives are also fully consistent with the vision of the National Research Council (NRC) which noted that exposure science will play a critical role in a new risk-based toxicity assessment framework. In this context, biomonitoring is a key component that quantitatively associates an internal dose with a measurable effect. It has also been suggested that epidemiology studies which accurately assess chemical exposures along with biological effects will have the most meaningful interpretation and thus maximal impact. However, a major impediment in conducting quantitative biomonitoring within epidemiology studies is the lack of rapid, sensitive, field deployable, quantitative technologies that measure chemical exposure/response biomarkers using minimally invasive biological fluids (i.e. saliva or drop of blood). Human exposure is rarely to single chemical agents but rather to complex chemical mixtures. This is particularly true in agriculture where multiple pesticides are utilized in combination and/or sequential application to crops. Due to the complex nature of occupational exposures and biological systems, measurement of a single biomarker may not provide adequate quantitative assessment of exposure. Hence, this project will undertake development, validation, and refinement of a novel multiplex sensor platform capable of quantifying multiple biomarkers associated with pesticide exposures (dose), utilizing saliva, blood or urine for biomonitoring. In addition, pharmacokinetic evaluations will be exploited to facilitate quantifying dosimetry. Hence, it is hypothesized that a multiplex biomarker sensor can be used to quantify mixed pesticide exposures (i.e. systemic dose) by measuring parent metabolites and cholinesterase (ChE) in biological samples. This project will specifically focus on the development of a multiplex sensor array for those pesticides and their metabolites that are known to be readily excreted in saliva and correlate with blood concentrations. Short-term outcomes of this research will include publication and presentation of research results; whereas, intermediate outcomes will focus on development/testing of a sensor platform with an eventual end outcome (beyond scope of current project) of using the sensor system for measuring and subsequently reducing worker exposure to pesticides. The development, validation and subsequent deployment of a multiplex sensor array platform as a quantitative tool to measure mixed pesticide occupational exposures is fully consistent with the goals of the NIOSH Research to Practice (r2P) initiative.